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Utility of Developmental Neurotoxicity In Vitro Battery to Address Regulatory Challenges (Syngenta SOT 24)
Citation:
Jackson, B., L. Minnema, C. Schlosser, A. Hofstra, K. Carstens, AND T. Shafer. Utility of Developmental Neurotoxicity In Vitro Battery to Address Regulatory Challenges (Syngenta SOT 24). Presented at SOT Conference 2024: A New Approach Method (NAM) to Screen for the Impact of Endogenous Stress on Chemical Toxicity, Salt Lake City, UT, March 10 - 14, 2024. https://doi.org/10.23645/epacomptox.25541578
Impact/Purpose:
Poster presented to SOT Conference 2024: A New Approach Method (NAM) to Screen for the Impact of Endogenous Stress on Chemical Toxicity
Description:
Background and Purpose: Limitations to the in vivo developmental neurotoxicity (DNT) test includes high variability, low reproducibility, and unknown human relevance. Moreover, neuropathological assessments in the DNT guideline are challenging due to methodology, lack of mechanistic understanding, and the high level of expertise required to conduct these assessments. The DNT in vitro battery (IVB) is a human-relevant, mechanistically informed alternative testing strategy that can be useful for screening and weight of evidence evaluations. This case study investigates the utility of the DNT IVB to inform uncertainties in an existing in vivo DNT study to refine toxicity endpoint selection for regulatory risk assessment. Methods: Acibenzolar-S-methyl was tested in the DNT IVB, and data were analyzed using the US EPA ToxCast Pipeline. Outcomes were examined in terms ofconsistency of evidence between assays assessing the same neurodevelopmental endpoint and with known biological relationships. Results of the battery were compared to in vivo results using an Integrated Approaches to Testing and Assessment (IATA) framework. Results: Examination of outcomes across the DNT IVB revealed that acibenzolar-S-methyl does not interact with key neurodevelopmental processes in vitro, such asproliferation, migration, apoptosis, differentiation, neurite maturation, synaptogenesis, and neural network connectivity. Conclusions: This case study highlights the ability of the DNT IVB to provide evidence to inform on potential DNT hazard without the need to conduct furthervertebrate testing. (This abstract does not reflect the policy of the US Environmental Protection Agency).
URLs/Downloads:
DOI: Utility of Developmental Neurotoxicity In Vitro Battery to Address Regulatory Challenges (Syngenta SOT 24)
TOXCAST_TOOLS_FOR_USERS_JAN2024_RAPID_ANSES.PDF (PDF, NA pp, 8468.852 KB, about PDF)